Tuesday, July 01, 2003

By Karen Hoffmann, Post-Gazette Staff Writer

The recent approval of an inhaled flu vaccine called FluMist by the Food and Drug Administration might signal not only the eventual demise of the flu shot, but also an accelerating shift to nasal sprays as a favored means of drug delivery.

Nasal sprays boast a number of advantages over other methods of administering drugs.

First of all, they get around people's fear of needles.

"If you compare nasal delivery to an injection, the patient is going to be more likely to accept [the nasal] route of delivery," said Dr. Denise Sokos, assistant professor of pharmacy and therapeutics at the University of Pittsburgh School of Pharmacy.

Nasal sprays let drugs reach the bloodstream rapidly and thus take effect more quickly. Viagra pills, for instance, can take up to an hour to work, causing some men to become impatient, take more of the anti-impotency drug and perhaps overdose. Researchers at the University of Kentucky in 1999 developed a form of Viagra that could be taken through the nose instead by pill and that works almost immediately.

Nasal sprays might also be used to deliver medications that can't be taken orally, such as insulin and other proteins that are destroyed in the stomach and intestine.

"The nasal route is very much in research right now because of proteins, and gene therapy, and large molecules," said Dr. Ashim Mitra, chairman of the Nasal Drug Delivery Focus Group of the American Association of Pharmaceutical Scientists. "Those are very difficult to deliver other than by giving injections."

Here's a look at advances and issues in the development of nasal delivery drugs:

Advantages

Nasal delivery offers particular advantages for vaccines. Injected vaccines cause an immune response throughout the body that provides protection from infection. Nasal delivery of vaccines not only produces this systemic immune response, but also a local immune response in the nasal lining, providing an additional barrier of protection.

"Many infectious diseases are transmitted via that mucosal route," Sokos explained.

Also, the nasal passages are rich in blood vessels, which makes it easier for the drug to be absorbed into the bloodstream and cause the systemic immune response.

The convenience of using a nasal spray for vaccination is another benefit. "In Third World countries, [nasal delivery] makes it very easy to vaccinate large populations without needing a needle," said Dr. Julie Suman, a graduate of Duquesne University and president of Next Breath LLC, a Baltimore company that does research on nasal delivery systems.

Challenges

The main problem with delivering drugs through a nasal spray is getting them to stick.

The nose is lined with mucus and tiny hairs called cilia. "The mucus is a defense mechanism that the body uses to keep out particles," said Suman. The cilia sweep the mucus to the back of the nasal cavity, where it is swallowed, about every 20 minutes. A lot of a nasally delivered drug thus gets swallowed and destroyed.

Ingredients are often added to sprays to help the drug stick to the nasal cavity and promote its absorption.

Insulin

Most diabetics would prefer an alternative to their daily injections of insulin. Companies like West Pharmaceuticals, Nastech, and France's INSERM are developing nasal delivery for insulin.

One of the main difficulties in nasal delivery of insulin is making sure the right dose is administered. "We're looking at a tremendous development in nasal delivery systems so that it accurately provides the dose," Mitra said.

Other hormones

While Americans can take nasal calcitonin for osteoporosis, Europeans have a wider array of hormones that can be taken as nasal sprays. "There are lots of products that are available in Europe that aren't on the U.S. market," Suman said. Among those are estrogen, testosterone, and leuprolide, a hormone suppressant.

"I've talked to a number of companies that are interested in bringing the products to the U.S.," she added.

Relieving pain

Another good candidate for nasal delivery is pain medication. Instead of swallowing a pill and waiting half an hour for pain relief, a nasal spray would relieve pain almost instantly.

"I think you're going to see a lot more medications for pain," said Suman. Several already are available for migraines, like GlaxoSmithKline's Imitrex and Magnum's Migranal.

Severe pain, like that experienced by cancer patients or following surgery, might be treated by nasal delivery of endorphins, the body's natural painkilling molecules.

Nose-to-brain

At the Nasal Drug Delivery Conference in London in March, Suman said, researchers heatedly debated whether it was possible to nasally administer drugs to the brain, such as nerve growth factor to treat Alzheimer's disease.

"We do not know exactly what governs the passage of the drug directly from the nose to the brain," Mitra said.

Some researchers claim that such a drug could be transported by the same nerve cells that allows us to smell.

"The hot topic is the delivery of a drug via the olfactory nerves into the brain," said Suman. "I've seen some studies that indicate that absorption can occur. Whether or not it's effective remains to be seen."

Karen Hoffmann can be reached at khoffmann@post-gazette.com or 412-263-1994.